Trauniatic brain injury often results in epilepsy that is poorly controlled by antiepileptic drugs. Although there is evitjence that axonal sproutingvenhanced excitatory synaptic connectivity and reduced inhibitory synaptic tranismisision are associated with posttraurriatic epileptogenesis, further information on how these changes occur and contribute to epileptogenesis is inconriplete. This information is crut^ial in providing a rational basis for the development of new therapies aimed to disrupt posttraumatic epileptogenesis. in the jai-pposed;study, I will use the partial cortical isolation (""""""""undercut"""""""") niodel and,a novel prganotypic slice culture model of posttraumatic epileptogenesis to investigate alterations in excitatory and inhibitory synaptic connectivity, Three specific questions will be addressed: (1) Does axonal sprouting play a critical role in posttraumatic epileptogienesis? (2) is there an incfeaise in excitatory synaptic coupling;between layer V pyramidal neurons after a chronic partial cortical isolation? I will use a combination of single and paired vvhole ceil recording, laser scanning photostimulation (LSP), transgenic mice, organotypic brain slice culture, gene gun transfectibn, and time-lapse confocal microscopy techniques. An LSP-guided dual whole cell recording tiechiiit^ue will be developed to improve efficiency of paired recordings. The resiilts of these experiments will identify and characterize alterations in excitatory synaptic transmission in the epileptogenic neocortex, document morphological dynamics during axonal sprouting after traumatic brain injury, and establish a novel in vitro model of posttraumatic epileptogenesis. Results from the pi'bposed study will contribute to a further understanding of normal synaptic circuitry and pathological ciianges involved in posttraumatic epilepsy and provide insights for- development of noveltherapies for preventing epileptogenesis after brain trauma.

Public Health Relevance

Traumatic brain injury often results in epileptic seizures'by causing stronger excitatory conhectiohs and/or weaker inhibitory connections between neurons of the brain. This research proposal will study how these changes occur* and provide insights for development of novel therapies for prevention and treatnrient of epilepsy after brain injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Transition Award (R00)
Project #
5R00NS057940-04
Application #
7835543
Study Section
Special Emphasis Panel (NSS)
Program Officer
Fureman, Brandy E
Project Start
2007-07-15
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$249,000
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Xiong, Wenhui; Ping, Xingjie; Ripsch, Matthew S et al. (2017) Enhancing excitatory activity of somatosensory cortex alleviates neuropathic pain through regulating homeostatic plasticity. Sci Rep 7:12743
Ping, Xingjie; Jin, Xiaoming (2016) Transition from Initial Hypoactivity to Hyperactivity in Cortical Layer V Pyramidal Neurons after Traumatic Brain Injury In Vivo. J Neurotrauma 33:354-61
Ping, Xingjie; Jin, Xiaoming (2016) Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice. PLoS One 11:e0158231
Ping, Xingjie; Jiang, Kewen; Lee, Seung-Young et al. (2014) PEG-PDLLA micelle treatment improves axonal function of the corpus callosum following traumatic brain injury. J Neurotrauma 31:1172-9
Xiong, Wenhui; Jin, Xiaoming (2012) Optogenetic field potential recording in cortical slices. J Neurosci Methods 210:119-24
Wilson, S M; Xiong, W; Wang, Y et al. (2012) Prevention of posttraumatic axon sprouting by blocking collapsin response mediator protein 2-mediated neurite outgrowth and tubulin polymerization. Neuroscience 210:451-66
Xiong, Wenhui; Ping, Xingjie; Gao, Jianhua et al. (2011) Preparing undercut model of posttraumatic epileptogenesis in rodents. J Vis Exp :
Jin, Xiaoming; Huguenard, John R; Prince, David A (2011) Reorganization of inhibitory synaptic circuits in rodent chronically injured epileptogenic neocortex. Cereb Cortex 21:1094-104